1. Field of the Invention
This invention relates to the field of pharmaceutical drug compositions used for implantation in a cavity produced by the surgical removal of tissue. In particular, the invention relates to a polymeric composition, having a macrophage activating additive and an accelerator, which is implanted in a surgically produced cavity, and which aids in regenerative tissue growth.
2. Description of Related Art
The local activation of macrophage elements, mobile white blood cells that capture and destroy bacteria and other foreign particles, can increase the proliferative activity of connective-tissue and promote homeostasis recovery.
It has been established that local activation of macrophage elements exert substantial influence in the control of tumor growth and metastatic spreading. Metastatic spreading refers to the transmission of tumor cells from the original site to one or more sites elsewhere in the body. Of course, one of the chief difficulties with effectively treating tumors is such spreading. Studies have been conducted regarding the possibility of activating macrophage elements by biological and chemical agents.
The activation of macrophage elements increases the activity of their lysosomal enzymes, intensifies the production of monokines affecting the processes of lymphocyte (white blood cells in the lymph) differentiation and activates cells of the fibroblastic tissue series. Macrophage activation also produces fibroblastic tissue series by extracellular matrix biopolymerics as well as intensifies the cytotoxic potential to the tumor cells.
It is also recognized that it may not be possible to remove all tumor cells when only the "tumor" itself is surgically removed. Unfortunately, any stray cells left behind may lead to recurrence of the tumor. In an attempt to avoid this problem, surgeons have removed not only the tumor itself but also the surrounding tissue which may contain stray tumor cells.
This approach may have several difficulties. First, it may necessitate surgically removing more surrounding tissue than is actually necessary to remove the tumor cells to ensure against recurrence. This may result in a rather large post-operative wound, for example, a large cavity in the tissue requiring a long period to heal. In addition, long term complications can result because of the relaxation of the immune system which controls proliferation, the growth by active cell division after a period of inactivity and by differentiation processes of the body. Also, the healing process may result in an unsightly permanent cavity where the tumor and surrounding tissue was removed.
It would be desirable to find a composition which could be applied to the tumor removal site after surgery to ensure eradication of any stray tumor cells. Additionally, it would be desirable if the composition included an alloplastic material to intensify regeneration of tissue such that a permanent cavity, would not remain when the healing process of the overlying tissue is complete.
Reference is made to Pharmacy, ISSN 0367-3014 No. 2, 1989, Moscow Medicine, "Extraction Spectrophotometric Determination of Levamisol Yield From Polymer-Based Long-Acting Drugs". In this publication, a procedure is disclosed for extraction of spectrophotometric determination of levamisole hydrochloride and solution. The agent was studied for time course of its yields from a polymer-based long-acting drug under the condition simulating an internal environment. Also relevant is the publication Reports of Academy of Scientists USSR, Kiev Series 3 Geology, Chemistry and Biological Science 1988 No. 2, "Biostructure of Cellular Method of Polyurethane Regulated By Levamisol". This publication discusses the effect of levamisole interaction into a urethane composition on the cellular method of biodegradation of the polymer base.
Kiev ISSN 0233-7657. Biopolymers and Cells, 1989, U.S., No. 4, "The Possibility Of Tissue Regeneration Intensification By The Increase In The Differentiation Degree Of Cell Elements And Conditions Of Tissue Defects," is another publication which discusses tests conducted on animals, primarily inbred rats and rabbits in which levamisole and its effect on the regeneration process was studied.
Reports of Academy of Sciences of the Ukranian SSR, Series B geological, Chemistry and Biological Sciences, 1989, No. 4, "Studies of the Reverse Processes in Tumor Growth on Local Application of the Polymer Preparation with the Prolonged Immunimodulating Effect," is a publication which discusses the mechanism of action of a composition having a prolonged immunomodulating effect.
Finally, reference is made to Experimental Oncology, ISSN 0204-3564 1991 Volume 13 No. 2, "Influence of Polymer Combination Including Levamisol on the Growth of Sarcoma 45." This article discusses the inhibition of growth of morphogenic features of sarcoma 45 with local administration of a polyurethane in combination with levamisol.